In our continuing x-ray diffraction studies of the various crystalline forms of the Staphylococcal nuclease, we now have in hand and are analyzing data that extends to 1.5A resolution for crystals of both the native and inhibited forms (ternary complex of nuclease plus thymidine-3',5'-diphosphate plus Ca2 ion). Crystals have been obtained and data collected with nuclease crystals containing various phosphonate analogues of thymidine dinucleotides. We would hope that this work will further delineate the extent of the nucleotide bending site of this enzyme. The structures of methylguanidinium mono- and dihydrogen phosphate have been shown to mimic the interaction among Arginines-35 and 87 of the nuclease and the 5' -phosphate of thymidine-3',5' diphosphate observed in the structure of inhibited nuclease crystals. Guanidinium ions have been shown to decrease the rate of hydrolysis of simple monoesters of phosphoric acid; we plan to extend this work to diesters in an attempt to find a simple model system that mimic the enzymatic mechanism of the nuclease. A new, efficient and highly economical approach to the refinement of the structural data from crystallographic studies on biological macromolecules is under development and test on our nuclease data as well as that of other known structures.